Hypercalcaemia

Serum calcium concentration is tightly regulated between 2.1-2.6mmol/L. Severe hypercalcaemia is a life-threatening electrolyte emergency requiring prompt recognition and urgent treatment.  

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Classification

  • Mild (2.65 – 3.00 mmol/L): Patient is often asymptomatic
  • Moderate (3.01-3.40 mmol/L): Can be asymptomatic or symptomatic
  • Severe (>3.40 mmol/L): Risk of dysrhythmia and coma

Serum calcium is found in 2 forms = either bound to albumin or free. A ‘corrected’ calcium takes into account the serum albumin level and so reflects a more accurate calcium level. Patients with suspected hypercalcaemia may have a ‘normal’ calcium level reported if their albumin is low.

Causes

Hyperparathyroidism & Malignancy account for 90% of cases of hypercalcaemia.

Hence PTH is incredibly helpful – in hyperparathyroidism it’ll be inappropriately high or normal & in malignancy, PTH is appropriately low.

Hyperparathyroidism is the most common cause in the community. There is an adenoma or hyperplasia of the parathyroid gland causing hypercalcaemia. Malignancy is the most common cause in hospitalised patients where PTHrP or bony metastases are typically the most common mechanisms for hypercalcaemia.

Suppressed/Low PTHHigh or Normal PTH
MalignancyPrimary hyperparathyroidism (adenoma)
Granulomatous diseaseTertiary hyperparathyroidism (chronic renal failure)
Drugs: Calcium and/or vitamin D supplements, Antacids, Thiazide diuretics, Lithium, Theophylline toxicityFamilial hypocalciuric hypercalcaemia (rare)
Rhabdomyolysis
Very Rarely – Adrenal insufficiency, Thyrotoxicosis, Phaeochromocytoma

Do note that secondary hyperparathyroidism is not a cause of hypercalcaemia. In this condition, there is an appropriate increase in PTH secretion secondary to hypocalcaemia as a result of chronic kidney disease.

Signs & Symptoms

‘Bones, stones, groans and psychic moans’

Chronic symptoms are more consistent with hyperparathyroidism, whereas a more recent onset of symptoms suggests malignancy. There may be other symptoms in keeping with the underlying cause e.g. red flags of malignancy.

Examination

  • Assess for cognitive impairment/GCS
  • Fluid balance status
  • Any specific examination if appropriate for an underlying cause e.g. lymph nodes, abdomen etc

Investigations

  • Bloods: bone profile (usually includes corrected calcium, phosphate, albumin), PTH, vitamin D, ALP, U&Es
  • ECG: Shortened QT interval → Bradycardia → 1st degree heart block
  • CXR
  • (Consider Serum ACE if sarcoidosis suspected)
CausePTHALPPhosphate
Primary or Tertiary hyperparathyroidismNormal/raisedNormal/raisedLow
Bone metastasesLowRaisedRaised
Myeloma, Vitamin D overdose or Granulomatous diseaseLowNormalRaised

Management

You should always discuss patients with hypercalcaemia with a senior

First Line: Rehydration = IV 0.9% sodium chloride 4-6L in 24 hours. Hypercalcaemia can cause significant dehydration. Monitor the fluid balance for pulmonary oedema.

Second Line: IV bisphosphonates (zoledronate or pamidronate as per local guidelines). The patient must be well-hydrated before use. It takes around 48-72 hours before a response is seen which lasts one to four weeks depending on the aetiology and other factors. Adverse effects include oesophagitis & osteonecrosis of the jaw.

Third Line: Dialysis in patients with severe hypercalcaemia, anuria (AKI or CKD) or where fluid overload is a likely issue. Alternatively, under specialist advice, cinacalcet (or other calcimimetics), denosumab or calcitonin. Prednisolone may be used in lymphoma, granulomatous disease or Vitamin D poisoning.

Loop diuretics may be used in those that cannot tolerate aggressive fluid hydration but are not very effective & must be used with caution, as they can worsen electrolyte disturbance & volume depletion.

Hyperparathyroidism

Endocrinologists will usually see these patients in clinics to decide if they are fit for surgery. If so, they’ll organise ultrasound or other imaging of the parathyroid glands. They will also need a 24-hour urine calcium collection to exclude FHH & DEXA scan to monitor osteoporosis.

References / Further Reading

By Dr Angela Yan (FY2), Dr Ruth Allen (FY1) & Dr Akash Doshi (ST4 Endocrinology)

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